| First Author | Oka M | Year | 2008 |
| Journal | Blood | Volume | 111 |
| Issue | 9 | Pages | 4571-9 |
| PubMed ID | 18310502 | Mgi Jnum | J:134339 |
| Mgi Id | MGI:3785340 | Doi | 10.1182/blood-2007-10-120337 |
| Citation | Oka M, et al. (2008) Inhibition of endogenous TGF-{beta} signaling enhances lymphangiogenesis. Blood 111(9):4571-9 |
| abstractText | Lymphangiogenesis is induced by various growth factors, including VEGF-C. Although TGF-beta plays crucial roles in angiogenesis, the roles of TGF-beta signaling in lymphangiogenesis are unknown. We show here that TGF-beta transduced signals in human dermal lymphatic microvascular endothelial cells (HDLECs) and inhibited the proliferation, cord formation, and migration toward VEGF-C of HDLECs. Expression of lymphatic endothelial cell (LEC) markers, including LYVE-1 and Prox1 in HDLECs, as well as early lymph vessel development in mouse embryonic stem cells in the presence of VEGF-A and C, were repressed by TGF-beta but were induced by TGF-beta type I receptor (TbetaR-I) inhibitor. Moreover, inhibition of endogenous TGF-beta signaling by TbetaR-I inhibitor accelerated lymphangiogenesis in a mouse model of chronic peritonitis. Lymphangiogenesis was also induced by TbetaR-I inhibitor in the presence of VEGF-C in pancreatic adenocarcinoma xenograft models inoculated in nude mice. These findings suggest that TGF-beta transduces signals in LECs and plays an important role in the regulation of lymphangiogenesis in vivo. |
